Saturday, October 8, 2016

Ref.: (LML) A Dual Crisis: The Chemotherapy of MB Leprosy and Leprosy Control

Leprosy Mailing List – September 20,  2016

Ref.:  (LML)   A Dual Crisis:   The Chemotherapy of MB Leprosy and Leprosy Control

From:  Robert Gelber, San Francisco, California





Dear Pieter,

As a background here and to add information to these comments, I, with the gracious permission of Paul Saunderson, wish to share as an attachment (15 MB) an editorial co-authored by myself and Jacques Grosset, published in Leprosy Review 2012, entitled:  “The Chemotherapy of Leprosy: An Interpretive History”.
There is a compelling literature that the therapy of MB leprosy and particularly in those with a high bacterial burden, whether it be with other rifampin-containing regimens or two-year WHO MDT, results in an unacceptably high relapse rate. 

That remains underappreciated and without address for several reasons: 
-       MB relapse following MDT and other rifampin-containing regimens appears first six years after the completion of therapy and most commonly ten or more years thereafter when patients are no longer accessing leprosy care, and, also, MB relapse is rarely associated with neuropathy or deformity.
-       Furthermore, MB relapse may not be reported because there is shame that non-compliance might have been its cause or a loss of confidence that the promised cure was not realized. 
-       Also, if a patient presents to another service provider, a history of prior treatment may not be elicited. 
-       Contributing to the lack of recognition of MB relapsed leprosy in the medical literature is that few studies, especially with the regular and prolonged follow-up required to assess the problem, have been conducted and published. 
-       Importantly, in the current climate where leprosy care is increasingly performed by the general health services, we found those services recognized considerably fewer relapses than those conducted by seasoned leprologists.
There is some reason for hope that an alternative MB MDT regimen might prove reliably curative.  This prospect should be urgently studied.  In fact, the short-term chemotherapy of tuberculosis required two bactericidal agents, where MB MDT contains but one, rifampin.   As moxifloxicin has proved both in mice and clinical trials to be equipotent to rifampin, a rifampin / moxifloxicin regimen, containing one or more other agents similarly proved more active than dapsone and clofaximine, might make a finite therapy of MB leprosy possible – a most important goal.  For this, WHO MDT has failed.  For that reason, I currently recommend for MB patients continued life-long dapsone treatment.

Unfortunately, for almost the past two decades, I know of no new studies for leprosy of the activity of antimicrobials in mice, particularly those active against M. tuberculosis and almost none in leprosy patients.   Clearly, chemotherapy studies have lost their import.  This is not surprising as the efficacy of MDT in all leprosy patients has largely been unchallenged.  Future studies should be a priority, but these are hindered as there are few mouse footpads worldwide to monitor them, and especially with the necessary experience and capacity.  If this is not urgently corrected, soon there may well be none at all and with the trained technologists having experience with the painstaking methodology of that system which has been largely unpublished.  Though several in vitro methods dedicated to replace the mouse footpad have some promise, none have been established anywhere near the sensitivity of the mouse footpad (one to a few bacilli).

On an entirely separate note, as we pointed out in the attachment for India, and as Karin Smith et al. demonstrated, occurred worldwide (PLOS Neglected Tropical Diseases, April 23, 2015), the dramatic fall in the incidence of new cases of leprosy by a factor of two or three in the five or six year period of 2000 – 2006, was not plausible.   The reason for this unreasonable fall in leprosy incidence must surely be loss of operational infrastructure.  Both the attachment and this referenced article point to the road to redress this frightening trend which will surely lead not only to delayed or absent treatment for millions, but the threat those untreated patients pose to infect others and to further heighten the leprosy burden.  Furthermore, the loss of infrastructure has importantly caused a greater incidence of deformity in the minority fortunate enough to have been recognized and placed on treatment.


Robert Gelber
University of California

LML - S Deepak, B Naafs, S Noto and P Schreuder

Contact: Dr Pieter Schreuder << editorlml@gmail.com >>.

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